Characterization of a Cell‐Penetrating Peptide with Potential Anticancer Activity

• Published in: ChemMedChem Vol. 12; no. 1; pp. 42 - 49
• Main Authors: Gronewold, Anja, Horn, Mareike, Ranđelović, Ivan, Tóvári, József, Muñoz Vázquez, Sergio, Schomäcker, Klaus, Neundorf, Ines
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 05.01.2017; John Wiley and Sons Inc
• Subjects: anticancer activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; cell-penetrating peptides; Cell-Penetrating Peptides - chemical synthesis; Cell-Penetrating Peptides - chemistry; Cell-Penetrating Peptides - pharmacology; Dactinomycin - chemical synthesis; Dactinomycin - chemistry; Dactinomycin - pharmacology; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; lytic peptides; Prescription drugs; Structure-Activity Relationship; tumor cells; tumor targeting; tumor targeting; lytic peptides; anticancer activity; tumor cells; cell-penetrating peptides
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201600498

Cell‐penetrating peptides (CPPs) are still an interesting and viable alternative for drug delivery applications. CPPs contain considerably high amounts of positively charged amino acids, imparting them with cationic character. Tumor cells are characterized by an enhanced anionic nature of their membrane surface, a property that could be used by CPPs to target these cells. We recently identified a branched CPP that displays a high internalization capacity while exhibiting selectivity for certain tumor cell types. In this study we elucidated this observation in greater detail by investigating the underlying mechanism behind the cellular uptake of this peptide. An additional cytotoxicity screen against several cancer cell lines indeed demonstrates high cytotoxic activity against cancer cells over normal fibroblasts. Furthermore, we show that this feature can be used for delivering the anticancer drug actinomycin D with high efficiency in the MCF‐7 cancer cell line. Positively charged! A cell‐penetrating peptide with preferential cytotoxic activity against tumor cells is presented. Cellular uptake is dependent on the cell lines used and their specific cell membrane composition. In this study we elucidated this observation in detail by investigating the underlying mechanisms behind this peptide′s cellular uptake. Additional cytotoxicity assays against several cancer cell lines showed high cytotoxic activity for cancer cells over normal fibroblasts.